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    HLCS holocarboxylase synthetase [ Homo sapiens (human) ]

    Gene ID: 3141, updated on 27-Nov-2024

    Summary

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    Official Symbol
    HLCSprovided by HGNC
    Official Full Name
    holocarboxylase synthetaseprovided by HGNC
    Primary source
    HGNC:HGNC:4976
    See related
    Ensembl:ENSG00000159267 MIM:609018; AllianceGenome:HGNC:4976
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HCS
    Summary
    This gene encodes an enzyme that catalyzes the binding of biotin to carboxylases and histones. The protein plays an important role in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. Defects in this gene are the cause of holocarboxylase synthetase deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jun 2011]
    Expression
    Ubiquitous expression in thyroid (RPKM 4.3), prostate (RPKM 3.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HLCS in Genome Data Viewer
    Location:
    21q22.13
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (36748625..36990211, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (35130819..35372426, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (38120926..38362511, complement)

    Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369308 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:38031419-38031920 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:38031921-38032420 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr21:38067894-38068806 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:38072642-38073235 Neighboring gene uncharacterized LOC107985492 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:38073236-38073828 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:38077313-38078142 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:38078973-38079802 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:38081463-38082292 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:38091813-38092599 Neighboring gene SIM bHLH transcription factor 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13289 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr21:38121986-38122511 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr21:38122512-38123036 Neighboring gene NANOG hESC enhancer GRCh37_chr21:38128709-38129210 Neighboring gene uncharacterized LOC105369305 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:38158985-38159520 Neighboring gene Sharpr-MPRA regulatory region 9348 Neighboring gene HLCS intron CAGE-defined mid-level expression enhancer Neighboring gene RNA, 5S ribosomal pseudogene 491 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr21:38281839-38283038 Neighboring gene Sharpr-MPRA regulatory region 2954 Neighboring gene ReSE screen-validated silencer GRCh37_chr21:38300053-38300245 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:38312167-38312666 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr21:38319174-38319727 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18441 Neighboring gene ReSE screen-validated silencer GRCh37_chr21:38338431-38338761 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13291 Neighboring gene divergent-paired related homeobox pseudogene 5 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13292 Neighboring gene HLCS antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13293 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13294 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:38378343-38378843 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13295 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18442 Neighboring gene mitochondrial ribosomal protein L20 pseudogene 1 Neighboring gene ripply transcriptional repressor 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Clinical and biochemical findings on a child with multiple biotin-responsive carboxylase deficiencies. Narisawa K, et al. J Inherit Metab Dis, 1982. PMID 6133032
    2. Effects of single-nucleotide polymorphisms in the human holocarboxylase synthetase gene on enzyme catalysis. Esaki S, et al. Eur J Hum Genet, 2012 Apr. PMID 22027809, Free PMC Article
    3. Human holocarboxylase synthetase with a start site at methionine-58 is the predominant nuclear variant of this protein and has catalytic activity. Bao B, et al. Biochem Biophys Res Commun, 2011 Aug 19. PMID 21802411, Free PMC Article
    4. Three promoters regulate the transcriptional activity of the human holocarboxylase synthetase gene. Xia M, et al. J Nutr Biochem, 2013 Nov. PMID 24075901, Free PMC Article
    5. Holocarboxylase synthetase is a chromatin protein and interacts directly with histone H3 to mediate biotinylation of K9 and K18. Bao B, et al. J Nutr Biochem, 2011 May. PMID 20688500, Free PMC Article

    See all (70) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CircRNA HLCS regulates lens epithelial cell apoptosis via miR-338-3p/BPNT1 axis.
      Title: CircRNA HLCS regulates lens epithelial cell apoptosis via miR-338-3p/BPNT1 axis.
    2. Biotin protein ligase as you like it: Either extraordinarily specific or promiscuous protein biotinylation.
      Title: Biotin protein ligase as you like it: Either extraordinarily specific or promiscuous protein biotinylation.
    3. Clinical, biochemical, and genetic analysis of 28 Chinese patients with holocarboxylase synthetase deficiency.
      Title: Clinical, biochemical, and genetic analysis of 28 Chinese patients with holocarboxylase synthetase deficiency.
    4. The function of HCS and biotin in metabolism and human disease, a putative role for the enzyme in histone biotinylation, and its participation as a nuclear factor in chromatin dynamics is discussed.
      Title: Holocarboxylase Synthetase: A Moonlighting Transcriptional Coregulator of Gene Expression and a Cytosolic Regulator of Biotin Utilization.
    5. The transcriptional function of HCS was shown by in vitro pull down and in vivo co-immunoprecipitation assays to depend on its interaction with the histone deacetylases HDAC1, HDAC2 and HDAC7
      Title: Holocarboxylase synthetase acts as a biotin-independent transcriptional repressor interacting with HDAC1, HDAC2 and HDAC7.
    6. Data suggest that direct interactions of HLCS (holocarboxylase synthetase) with NCOR1 (nuclear receptor corepressor 1) and HDAC1 (histone deacetylase 1) contribute toward transcriptional repression of repeats, presumably increasing genome stability.
      Title: Holocarboxylase synthetase interacts physically with nuclear receptor co-repressor, histone deacetylase 1 and a novel splicing variant of histone deacetylase 1 to repress repeats.
    7. study characterizes three functional promoters in the human HLCS gene
      Title: Three promoters regulate the transcriptional activity of the human holocarboxylase synthetase gene.
    8. HLCS interacts physically with the DNA methyltransferase DNMT1 and the methyl CpG binding protein MeCP2 to facilitate the binding of HLCS to chromatin.
      Title: Holocarboxylase synthetase synergizes with methyl CpG binding protein 2 and DNA methyltransferase 1 in the transcriptional repression of long-terminal repeats.
    9. This study showed that modification of HSP72 and demonstrated that binding of biotin to extracellular HSP72 prepares cells for a strong immune response.
      Title: Holocarboxylase synthetase catalyzes biotinylation of heat shock protein 72, thereby inducing RANTES expression in HEK-293 cells.
    10. individuals with HLCS SNPs may benefit from supplemental biotin, yet to different extents depending on the genotype
      Title: Effects of single-nucleotide polymorphisms in the human holocarboxylase synthetase gene on enzyme catalysis.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Holocarboxylase synthetase deficiency
    MedGen: C0268581 OMIM: 253270 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables biotin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables biotin--[biotin carboxyl-carrier protein] ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables biotin--[biotin carboxyl-carrier protein] ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables biotin--[biotin carboxyl-carrier protein] ligase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables biotin--[biotin carboxyl-carrier protein] ligase activity TAS
    Traceable Author Statement
    more info
    		  
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in biotin metabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in post-translational protein modification IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to biotin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol HDA PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nuclear lamina IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    biotin--protein ligase
    Names
    biotin apo-protein ligase
    biotin--[acetyl-CoA-carboxylase] ligase
    biotin--[methylcrotonoyl-CoA-carboxylase] ligase
    biotin--[methylmalonyl-CoA-carboxytransferase] ligase
    holocarboxylase synthetase (biotin-(proprionyl-CoA-carboxylase (ATP-hydrolysing)) ligase)
    holocarboxylase synthetase (biotin-(proprionyl-Coenzyme A-carboxylase (ATP-hydrolysing)) ligase)
    NP_000402.3
    NP_001229713.1
    NP_001229714.1
    NP_001339443.1
    NP_001339444.1
    NP_001339445.1
    NP_001339446.1
    NP_001339447.1
    XP_011527842.1
    XP_024307833.1
    XP_047296708.1
    XP_047296709.1
    XP_047296710.1
    XP_047296711.1
    XP_047296712.1
    XP_054180425.1
    XP_054180426.1
    XP_054180427.1
    XP_054180428.1
    XP_054180429.1
    XP_054180430.1
    XP_054180431.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016193.2 RefSeqGene

      Range
      28726..246769
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000411.8 → NP_000402.3  biotin--protein ligase isoform 1

      See identical proteins and their annotated locations for NP_000402.3

      Status: REVIEWED

      Source sequence(s)
      AP000697, D23672, D87328
      Consensus CDS
      CCDS13647.1
      UniProtKB/Swiss-Prot
      B2RAH1, D3DSG6, P50747, Q99451
      UniProtKB/TrEMBL
      A0A6Q8PFK4
      Related
      ENSP00000338387.3, ENST00000336648.8
      Conserved Domains (3) summary
      pfam02237
      Location:669 → 716
      BPL_C; Biotin protein ligase C terminal domain
      cd16442
      Location:467 → 647
      BPL; biotin protein ligase
      cl00020
      Location:202 → 460
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    2. NM_001242784.3 → NP_001229713.1  biotin--protein ligase isoform 1

      See identical proteins and their annotated locations for NP_001229713.1

      Status: REVIEWED

      Source sequence(s)
      AP000697, AP000698, AP000704, D87328, DB290499
      Consensus CDS
      CCDS13647.1
      UniProtKB/Swiss-Prot
      B2RAH1, D3DSG6, P50747, Q99451
      UniProtKB/TrEMBL
      A0A6Q8PFK4
      Related
      ENSP00000382071.1, ENST00000399120.5
      Conserved Domains (3) summary
      pfam02237
      Location:669 → 716
      BPL_C; Biotin protein ligase C terminal domain
      cd16442
      Location:467 → 647
      BPL; biotin protein ligase
      cl00020
      Location:202 → 460
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    3. NM_001242785.2 → NP_001229714.1  biotin--protein ligase isoform 1

      See identical proteins and their annotated locations for NP_001229714.1

      Status: REVIEWED

      Source sequence(s)
      AP000697, AP000698, AP000702, AP000703, AP000704
      Consensus CDS
      CCDS13647.1
      UniProtKB/Swiss-Prot
      B2RAH1, D3DSG6, P50747, Q99451
      UniProtKB/TrEMBL
      A0A6Q8PFK4
      Related
      ENSP00000479939.1, ENST00000612277.4
      Conserved Domains (3) summary
      pfam02237
      Location:669 → 716
      BPL_C; Biotin protein ligase C terminal domain
      cd16442
      Location:467 → 647
      BPL; biotin protein ligase
      cl00020
      Location:202 → 460
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    4. NM_001352514.2 → NP_001339443.1  biotin--protein ligase isoform 2

      Status: REVIEWED

      Source sequence(s)
      AP000697, AP000698, AP000702, AP000703, AP000704
      Consensus CDS
      CCDS93094.1
      UniProtKB/TrEMBL
      A0A8C8QSB1
      Related
      ENSP00000502087.2, ENST00000674895.3
      Conserved Domains (3) summary
      pfam02237
      Location:816 → 863
      BPL_C; Biotin protein ligase C terminal domain
      cd16442
      Location:614 → 794
      BPL; biotin protein ligase
      cl00020
      Location:349 → 607
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    5. NM_001352515.2 → NP_001339444.1  biotin--protein ligase isoform 1

      Status: REVIEWED

      Source sequence(s)
      AP000697, AP000698, AP000702, AP000703, AP000704
      Consensus CDS
      CCDS13647.1
      UniProtKB/Swiss-Prot
      B2RAH1, D3DSG6, P50747, Q99451
      UniProtKB/TrEMBL
      A0A6Q8PFK4
      Related
      ENSP00000501832.1, ENST00000675057.1
      Conserved Domains (3) summary
      pfam02237
      Location:669 → 716
      BPL_C; Biotin protein ligase C terminal domain
      cd16442
      Location:467 → 647
      BPL; biotin protein ligase
      cl00020
      Location:202 → 460
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    6. NM_001352516.2 → NP_001339445.1  biotin--protein ligase isoform 1

      Status: REVIEWED

      Source sequence(s)
      AP000697, AP000698, AP000702, AP000703, AP000704
      Consensus CDS
      CCDS13647.1
      UniProtKB/Swiss-Prot
      B2RAH1, D3DSG6, P50747, Q99451
      UniProtKB/TrEMBL
      A0A6Q8PFK4
      Related
      ENSP00000501750.1, ENST00000675307.1
      Conserved Domains (3) summary
      pfam02237
      Location:669 → 716
      BPL_C; Biotin protein ligase C terminal domain
      cd16442
      Location:467 → 647
      BPL; biotin protein ligase
      cl00020
      Location:202 → 460
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    7. NM_001352517.1 → NP_001339446.1  biotin--protein ligase isoform 1

      Status: REVIEWED

      Source sequence(s)
      AP000697, AP000698, AP000702, AP000703, AP000704
      Consensus CDS
      CCDS13647.1
      UniProtKB/Swiss-Prot
      B2RAH1, D3DSG6, P50747, Q99451
      UniProtKB/TrEMBL
      A0A6Q8PFK4
      Conserved Domains (3) summary
      pfam02237
      Location:669 → 716
      BPL_C; Biotin protein ligase C terminal domain
      cd16442
      Location:467 → 647
      BPL; biotin protein ligase
      cl00020
      Location:202 → 460
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    8. NM_001352518.2 → NP_001339447.1  biotin--protein ligase isoform 1

      Status: REVIEWED

      Source sequence(s)
      AP000697, AP000698, AP000702, AP000703, AP000704
      Consensus CDS
      CCDS13647.1
      UniProtKB/Swiss-Prot
      B2RAH1, D3DSG6, P50747, Q99451
      UniProtKB/TrEMBL
      A0A6Q8PFK4
      Conserved Domains (3) summary
      pfam02237
      Location:669 → 716
      BPL_C; Biotin protein ligase C terminal domain
      cd16442
      Location:467 → 647
      BPL; biotin protein ligase
      cl00020
      Location:202 → 460
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    RNA

    1. NR_148020.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP000697, AP000698, AP000702, AP000703, AP000704

    2. NR_148021.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP000697, AP000698, AP000702, AP000703, AP000704

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

      Range
      36748625..36990211 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024452065.2 → XP_024307833.1  biotin--protein ligase isoform X4

      UniProtKB/TrEMBL
      A0A6Q8PFK4
      Conserved Domains (3) summary
      pfam02237
      Location:612 → 659
      BPL_C; Biotin protein ligase C terminal domain
      cd16442
      Location:410 → 590
      BPL; biotin protein ligase
      cl00020
      Location:145 → 403
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    2. XM_047440752.1 → XP_047296708.1  biotin--protein ligase isoform X1

    3. XM_047440754.1 → XP_047296710.1  biotin--protein ligase isoform X3

      UniProtKB/Swiss-Prot
      B2RAH1, D3DSG6, P50747, Q99451

    4. XM_047440753.1 → XP_047296709.1  biotin--protein ligase isoform X2

    5. XM_047440756.1 → XP_047296712.1  biotin--protein ligase isoform X7

    6. XM_011529540.3 → XP_011527842.1  biotin--protein ligase isoform X5

      Conserved Domains (1) summary
      cl00020
      Location:349 → 607
      GAT_1; Type 1 glutamine amidotransferase (GATase1)-like domain

    7. XM_047440755.1 → XP_047296711.1  biotin--protein ligase isoform X6

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060945.1 Alternate T2T-CHM13v2.0

      Range
      35130819..35372426 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054324453.1 → XP_054180428.1  biotin--protein ligase isoform X4

    2. XM_054324450.1 → XP_054180425.1  biotin--protein ligase isoform X1

    3. XM_054324452.1 → XP_054180427.1  biotin--protein ligase isoform X3

      UniProtKB/Swiss-Prot
      B2RAH1, D3DSG6, P50747, Q99451

    4. XM_054324451.1 → XP_054180426.1  biotin--protein ligase isoform X2

    5. XM_054324456.1 → XP_054180431.1  biotin--protein ligase isoform X7

    6. XM_054324454.1 → XP_054180429.1  biotin--protein ligase isoform X5

    7. XM_054324455.1 → XP_054180430.1  biotin--protein ligase isoform X6

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P50747.1 GenPept UniProtKB/Swiss-Prot:P50747

    Gene LinkOut

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